Molecular Characterization of Peritoneal Involvement in Primary Colon and Ovary Neoplasm: The Possible Clinical Meaning of the P2X7 Receptor-Inflammasome Complex

Abstract

Introduction: Colon cancer (CC) and epithelial ovarian cancer (EOC) are common and severe neoplasms frequently sharing a massive inflammatory involvement of peritoneum. A detailed molecular characterization of such carcinomatosis has not been performed, so far. Methods: Omental adipocytes were isolated from thirty-three adult women who underwent primary surgery for CC or EOC. Expression of several pro-inflammatory genes was determined by real-time PCR and immunofluorescence. Data were related to the clinical phenotype of the patients. Results: CD68, FGFR1, and IL-6 were significantly more expressed in adipocytes from CC patients and VEGF in adipocytes from EOC. TNFα, TGFβ, or MCP-1, as well as the pro-inflammatory platform P2X7R-NLRP3, did not differ between the 2 cancers. White blood cell count, mirroring systemic inflammation, was related to adipocyte P2X7R (R = 0.508, p = 0.003), NLRP3 (R = 0.405; p = 0.02), and MCP-1 (R = 0.448; p = 0.009). P2X7R and NLRP3 were the only inflammatory factors significantly more expressed in patients carrying both omental and peritoneal carcinosis, who were also characterized by a higher leukocytosis. None of the tested inflammatory markers was associated with tumor grading for both neoplasms; however, the presence of metastases was associated with a higher adipocyte expression of FGFR1 and TGFβ. Conclusion: We show here that rarely measured molecules seem to specifically characterize omental carcinomatosis of CC or EOC, while more common inflammatory agents like TNFα, TGFβ, or MCP-1 do not; the P2X7R-NLRP3 complex marks omental and peritoneal carcinosis and is related to circulating white blood cells and MCP-1, involved in monocyte-macrophage tissue infiltration; increased TGFβ and FGFR1 characterize the tumoral dissemination.